Conformational analyses of thiamin-related compounds. A stereochemical model for thiamin catalysis

Conformational analyses of some thiamin-related compounds have been performed in order to find the relationship between their conformational and biochemical properties. Relaxed 2-D potential energy maps of free thiamin, its antagonists, and C(2) adducts were obtained using the molecular mechanics (MM) method. The antagonists include 4'-deaminothiamin, oxythiamin, pyrithiamin, thiamin thiaxolone, thiamin thiothiaxolone, 6'-methyl-4H-thiamin and 6'-methylthiamin, and the C(2) adducts include 2-(α-hydroxyethyl)thiamin (HET), 2-(α-lactyl)thiamin (LT), 6'-methyl-4H-lactylthiamin and 6'-methyllactylthiamin. All of the local minima conformers were also identified for the active intermediates LT and HET